Recent observations made in our laboratory and by others suggest that defects in development of the fine structure of cerebral cortex, especially of terminal axons, synapses and dendrites, form the anatomic basis in some cases of mental retardation. The present study is designed to further explore this finding. Dendritic development in brains from the retarded will be studied by use of the Golgi-Cox method. Whenever possible, cases in whom the etiology of the mental defect is known will be selected for study. Frontal cortex, hippocampus, and neocerebellar cortex will be examind. Extent of dendritic branching will be assessed by use of the quantitative Golgi method. In addition, the adaptability of the Blood Aghajanian electron-microscopic method for synapses to human postmortem brain tissue will be explored. Synapse counts will be obtained from areas adjacent to those studied by the Golgi-Cox technique. Ganglioside sialic acid and activity of Na ion -K ion ATPase- two possible biochemical markers for neuronal and synaptic membranes-will be measured in the same brain areas. It is hoped that from these studies will emerge patterns of developmental defect which will provide a neuropathologic basic for cases of mental retardation that fail to show significant lesions by gross examination or by standard light microscopy. The data also should provide further information regarding the special vulnerability of developing cerebral cortex. BIBLIOGRAPHIC REFERENCES: Huttenlocher, P.R. Synaptic and Dendritic Development and Mental Defect, in Brain Mechanisms in Mental Retardation, Buchwald and Brazier, Editors, Academic Press, 1975, pp. 123-140.